SAT0119 PARADOXICAL NEUTROPHIL ACTIVATION BY ANTI-IL6 THERAPY: TRANSCRIPTOME ANALYSIS SHOWS A RATIONALE FOR DERMATOLOGICAL ADVERSE REACTIONS AND DECREASED NEUTROPHIL COUNTS AFTER TOCILIZUMAB TREATMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 993.1-994
Author(s):  
M. Sakamoto ◽  
A. Senoh ◽  
Y. Sato ◽  
H. Iijima ◽  
M. Yamaguchi ◽  
...  
Keyword(s):  
Side Effects ◽  
Peripheral Blood ◽  
Side Effect ◽  
Neutrophil Migration ◽  
Neutrophil Activation ◽  
The Other ◽  
Leukocyte Migration ◽  
Other Hand ◽  
Serious Infections ◽  
Go Terms

Background:Skin rashes as a side effect of Tocilizumab therapy (TCZ- Tx) has not been paid much attention, because the incidence was only 1~2% in the drug information sheets. However, we experienced several RA cases with development of various skin rashes associated with neutrophil activation after TCZ-Tx. On the other hand, it is well known that the neutrophil counts in peripheral blood decreases after TCZ-Tx, whereas it does not affect the rate of serious infections. The detailed mechanism is still unclear.Objectives:To detect the characteristics of the changes in gene expressions of peripheral blood associated with TCZ-Tx and the development of skin rashes as its side effect.Methods:Total of 14 RA patients with TCZ-Tx were included. Among them, 4 patients developed TCZ-related rashes (group S) and 10 patients did not show any side effects (group C). Peripheral whole blood at just before (pre) and 3 months after (post) TCZ-Tx from each patient were subjected to the analysis. Total RNAs were extracted with PAXgene miRNA kit and analyzed with next-generation sequencing. First, group C was investigated for the normal response to TCZ-Tx. Differentially expressed genes (DEGs) were selected by paired comparison (post vs. pre). And then, enrichment analysis using gene ontology (GO) terms were performed. Second, to explore the characteristics of group S, all expressed genes in 14 cases at just before TCZ-Tx were subjected to a hierarchical clustering analysis. The DEGs (group S vs. C and post vs. pre) were also investigated with weighted gene co-expression network analysis (WGCNA) and GO analysis. Meanwhile, the total eigengene expressions of the important modules identified by WGCNA in each cases were also calculated.Results:Surprisingly, 8 out of the top 10 enriched GO terms in the up-regulated genes were relevant to leukocyte activation such as ‘neutrophil migration” by the analysis of DEGs (post vs. pre) in group C. The cluster analysis of ‘pre’ genes confirmed that the patterns of gene expression between group S and C was different. WGCNA analysis of DEGs (group S vs. C) revealed that genes related to acute inflammation such as ‘leukocyte mediated immunity’ were activated in group S. Interestingly, it was not correlated with disease activity score (DAS) of RA. By the analysis of DEGs (post vs. pre) of upregulated genes, we found that the total eigengene expressions of the module enriched with genes related to ‘cell adhesion’ or ‘leukocyte migration’ were significantly increased in all cases of group S.Conclusion:This is the first evidence that the genes associated with neutrophil migration is significantly activated after TCZ-Tx. It is noteworthy that the gene activation was observed in cases without any side effects. The decreased neutrophil counts in peripheral blood have been known after initiation of TCZ-Tx, which did not affect the rate of serious infections. Recently, It was reported that TCZ affects neutrophil trafficking to the bone marrow1). Our findings will provide a rationale for its cause. On the other hand, we experienced several RA cases with development of various skin rashes associated with neutrophil activation after TCZ-Tx. However, majority of patients do not develop the side effect, even though genes related to ‘neutrophil migration’ are activated. In group S, our findings indicate that the genes related to ‘leukocyte mediated immunity’ was already activated at the initiation of treatment without correlating to DAS of RA, furthermore, the gene upregulation related to ‘leukocyte migration’ was more prominent after TCZ-Tx. Although it is difficult to predict the patients developing skin rashes before TCZ-Tx, we do not recommend to use TCZ for the patients with neutrophilic dermatosis which is often associated with RA.References: :[1]Lok LSCet al.,Eur J Clin Invest. 47(10):736-745 (2017).Disclosure of Interests: :Moe Sakamoto: None declared, Akemi Senoh: None declared, Yoshiharu Sato: None declared, Hiroshi Iijima: None declared, Mari Yamaguchi: None declared, Toshie Higuchi: None declared, Yoshinobu Koyama Grant/research support from: Eli-Lilly and Mochida., Speakers bureau: BMS, Ayumi, Chugai, Ono, Mitsubishi Tanabe, Abbvie and Eisai.

The Nocebo Effect and Informed Consent—Taking Autonomy Seriously

2020 ◽  
Vol 29 (2) ◽  
pp. 223-235
Author(s):  
SCOTT GELFAND
Keyword(s):  
Informed Consent ◽  
Side Effects ◽  
Medical Treatment ◽  
Side Effect ◽  
Patient Autonomy ◽  
The Other ◽  
Nocebo Effect ◽  
Other Hand ◽  
Patient Will ◽  
Practical Tool

AbstractThe nocebo effect, a phenomenon whereby learning about the possible side effects of a medical treatment increases the likelihood that one will suffer these side effects, continues to challenge physicians and ethicists. If a physician fully informs her patient as to the potential side effects of a medicine that may produce nocebogenic effects, which is usually conceived of as being a requirement associated with the duty to respect autonomy, she risks increasing the likelihood that her patient will experience these side effects and therefore suffer (unnecessary) harm, a violation of the duty of nonmaleficence. If, on the other hand, she intentionally withholds side effect information in an effort to protect her patient from suffering unnecessary harm from side effects, which is consistent with the duty of nonmaleficence, she violates the duty to respect patient autonomy. In this paper, the author discusses several previous attempts to deal with the nocebo effect and explains their weaknesses. He then proposes a means of managing the nocebo effect and argues that it does not share the weaknesses found in previous approaches. He concludes with a discussion of a simple, yet practical tool that might help clinicians manage the tension resulting from the nocebo effect.

Management of Side Effects of Antidepressant Medications

Depression ◽  
2019 ◽  
pp. 241-256
Author(s):  
Rajnish Mago
Keyword(s):  
Side Effects ◽  
High Risk ◽  
Side Effect ◽  
Substantial Effect ◽  
The Other ◽  
Antidepressant Medications ◽  
Other Hand ◽  
Considerable Impact

Side effects of antidepressants are common, distressing, and impairing. They have a substantial effect on nonadherence to antidepressants, which is very common. Greater attention to learning about various strategies for preventing, reducing, and managing side effects may have a significant effect in improving the outcomes of treatment with antidepressants. Attention needs to be paid to both common, “nuisance” side effects and the uncommon or rare “medically serious” side effects. This chapter provides examples of both categories. While nuisance side effects may seem unimportant, in fact, they have a considerable impact on nonadherence. On the other hand, while medically serious side effects may be seen as uncommon or even rare, they can lead to serious consequences. In particular, clinicians who often treat patients who are at high risk of such medically serious side effects need to be thoroughly familiar with them. Clinicians who prescribe antidepressant medications are urged to have a menu of options for the management of side effects, ranging from simple, benign interventions to more active interventions that may carry risks of their own. The latter are often needed in situations where continuing that particular antidepressant, or type of antidepressant, is essential and stopping or changing it is not a reasonable option. In such situations, risk/benefit considerations require that the side effect be actively treated to allow the patient to stay on the medication. This chapter provides many examples of both simple and more active interventions for a variety of potential side effects of antidepressants.

CORTICOTROPIN-BESTIMMUNG ANHAND DES CORTICOSTERONANSTIEGES IM NEBENNIEREN-VENENBLUT HYPOPHYSEKTOMIERTER RATTEN

1962 ◽  
Vol 41 (2) ◽  
pp. 211-218 ◽  
Author(s):  
K. Retiene ◽  
H. Ditschuneit ◽  
M. Fischer ◽  
K. Kopp ◽  
E. F. Pfeiffer
Keyword(s):  
Peripheral Blood ◽  
Single Injection ◽  
Venous Blood ◽  
Corticosterone Level ◽  
The Other ◽  
Adrenal Vein ◽  
Major Surgery ◽  
Other Hand ◽  
Hypophysectomized Rats

ABSTRACT Corticotrophin has been measured by using the corticotrophin-induced increase of corticosterone in adrenal venous blood of rats, the corticotrophin secretion of which has been blocked by preliminary injection of dexamethasone. Sensitivity and precision of this technique have not been higher than in the simpler procedure using corticosterone increase in peripheral blood. Single injection of dexamethasone on the other hand did not prevent release of endogenous corticotrophin following major surgery, required for canulation of the adrenal vein. In hypophysectomized rats corticotrophin can be measured by using adrenal venous blood. 0.05 mU corticotrophin (US-P-Standard) has been determined with an index of precision of λ = 0.13. The consistent relation between initial and elevated corticosterone level following corticotrophin in both peripheral and adrenal venous blood makes it highly unlikely that other modifications of this kind of assay will increase sensitivity.

scholarly journals AKTUALISASI REVOLUSI MENTAL DALAM PENGELOLAAN DANA DESA (ANALISIS TAFSIR EKONOMI Q.S.YUSUF [12]: 55)

2020 ◽  
Vol 5 (2) ◽  
pp. 226-246
Author(s):  
Muhammad Amin ◽  
Azima Azima
Keyword(s):  
Side Effects ◽  
The Other ◽  
Other Hand ◽  
The Village

Dana Desa are one of the most effective policies in village development with the completion of various kinds of infrastructure in the village. On the other hand, this policy caused side effects in the form of criminal acts of corruption against these funds. Through the interpretation of Q.S. Yusuf verse 55, the author offers the actualization of the spirit of mental revolution in the management of village funds through measures to strengthen integrity, increase professionalism, innovation, responsibility, and broaden horizons. Through these steps, the village fund policy can be implemented completely and right on target.

scholarly journals On the issue of asepsis during laparotomy

1892 ◽  
Vol 6 (9) ◽  
pp. 825-845
Author(s):  
M. Mirenov
Keyword(s):  
Side Effects ◽  
The Other ◽  
Clinical Observations ◽  
Other Hand ◽  
The One

Clinical observations of recent years, showing, on the one hand, that the use of the antiseptic method in surgery often has undesirable side effects both on the patient's body and on the operating person himself; on the other hand, the excellent results obtained by surgeons who do not use the antiseptic method and observe only cleanliness have compelled operators with well-established clinics to replace antiseptics with asepsis more and more.

Is gabapentin effective for preventing delayed nausea and vomiting (NV) after moderately and highly emetogenic chemotherapy (CT)?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18575-18575
Author(s):  
A. Menendez-Leal ◽  
C. Quijano ◽  
A. G. Menendez-Rivera
Keyword(s):  
Side Effects ◽  
Primary Endpoint ◽  
Emetogenic Chemotherapy ◽  
The Other ◽  
Nausea And Vomiting ◽  
Highly Emetogenic Chemotherapy ◽  
Good Tolerability ◽  
Other Hand ◽  
Delayed Nausea ◽  
Financial Relationships

18575 Background: Following previous institutional observations,this protocol was designed to evaluate the efficacy of Gabapentin in the prophylaxis of delayed CT induced NV. Methods: The main elegibility criteria was moderate and severe NV on previous CT cycles.Gabapentin 300 mg caps. was given as follows: One capsule day -2, two capsules day -1 and one capsule tid from days 1 to 5. 24 pats. were evaluated; 22 (92%) female, 2 (8%) male.CT included Doxorubicin/Ciclofosfamide 15 (62.5%), Cis-Platin 5 (21%), Other regimens 4 (17%). Previous prophylaxis for all pats. included a 5-HT3 Antagonist plus Dexametasone. Pats. were instructed to complete a two-page Questionaire: On page 1 pats. indicated the intensity of nausea according a scale shown there. On page two they indicated the number of vomits they had.This was made three times daily for five days. The primary endpoint was reduction of NV aftyer CT. Results: The reduction observed in the number of vomits was as follows: Number of pats. that experienced 0 Vomits: day 1 (CT): 14 (58.3%); day 2: 18 (75%); day 3: 20 (83.3%); day 4: 18 (75%); day 5: 22 (91.7%). On the other hand, pats. that did not respond and had three or more vomits daily: day 1: 5 (20.8%); day 2: 2 (8.3%); day 3: 1 (4.2%); day 4: 3 (12.5%); day 5: 2 (8.3%).Most pats. experienced a decrease in the intensity of nausea as well. No significant side effects were seen. Conclusions: Gabapentin seems to have some efficacy preventing delayed NV after moderately and highly emetogenic CT. These results together with it’s possible effect on acute NV and good tolerability warrant further studies. No significant financial relationships to disclose.

The Initiation of Long-Term Pharmacotherapy in Schizophrenia: Dosage and Side Effect Comparisons Between Oral and Depot Fluphenazine*

1976 ◽  
Vol 09 (04) ◽  
pp. 159-169 ◽  
Author(s):  
Nina R. Schooler ◽  
J. Levine ◽  
Keyword(s):  
Side Effects ◽  
Side Effect ◽  
Dosage Forms ◽  
The Other ◽  
Oral Drug ◽  
Double Blind ◽  
Moderate Severity ◽  
Treatment Groups ◽  
The Relationship

SummaryThis report focuses on two comparisons between oral and depot fluphenazine specifically FPZ decanoate: 1) can equivalent dosages for the two drugs be established and do these equivalencies change over six months of treatment; 2) what are the side effects seen with the two drugs during the early weeks of administration.Patients in the study receive either oral or depot FPZ as the active treatment but in order to preserve double blind conditions, they are also given the other treatment in placebo form. No dosage equivalence is established by the protocol, however, if dosage is adjusted, both forms must be changed and in the same direction. During the first weeks of treatment there is a linear relationship between the two dosage forms but a range of relatively low dosages of the oral compound (5-20 mg) is associated with a single dose (25 mg/q 3 weeks) of FPZ decanoate. At higher dosages of the oral drug the relationship is linear. Side effects of some kind are noted in over 60 percent of patients in both treatment groups after four weeks of treatment, while symptoms of at least moderate severity occur in almost 40 percent. Only symptoms involving the extrapyramidal system and sleep disturbance are observed in more than 20 percent of the patients. Benztropine was prescribed only if needed and was administered to 65 percent of patients. In general, those receiving benztropine had more side effects than those who did not. These differences reached significance for extrapyramidal symptoms and depression.Based on these data, we conclude that at the dosages used in this study there are no side effect differences between these two forms of fluphenazine in the early weeks of administration. Dosage equivalence between the two drugs can be set within the range of 5- 60 mg/day oral and 12.5-100 mg/three weeks depot.

scholarly journals Understanding the basis of space closure in Orthodontics for a more efficient orthodontic treatment

2016 ◽  
Vol 21 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Gerson Luiz Ulema Ribeiro ◽  
Helder B. Jacob
Keyword(s):  
Side Effects ◽  
Orthodontic Treatment ◽  
Treatment Options ◽  
The Other ◽  
Advantages And Disadvantages ◽  
Other Hand ◽  
Space Closure ◽  
Sliding Mechanics

ABSTRACT Introduction: Space closure is one of the most challenging processes in Orthodontics and requires a solid comprehension of biomechanics in order to avoid undesirable side effects. Understanding the biomechanical basis of space closure better enables clinicians to determine anchorage and treatment options. In spite of the variety of appliance designs, space closure can be performed by means of friction or frictionless mechanics, and each technique has its advantages and disadvantages. Friction mechanics or sliding mechanics is attractive because of its simplicity; the space site is closed by means of elastics or coil springs to provide force, and the brackets slide on the orthodontic archwire. On the other hand, frictionless mechanics uses loop bends to generate force to close the space site, allowing differential moments in the active and reactive units, leading to a less or more anchorage control, depending on the situation. Objective: This article will discuss various theoretical aspects and methods of space closure based on biomechanical concepts.

The influence of age on lithium efficacy and side-effects in out-patients

1983 ◽  
Vol 13 (1) ◽  
pp. 53-60 ◽  
Author(s):  
N. Murray ◽  
S. Hopwood ◽  
D. J. K. Balfour ◽  
S. Ogston ◽  
D. S. Hewick
Keyword(s):  
Side Effects ◽  
Side Effect ◽  
Lithium Treatment ◽  
The Other ◽  
Hand Tremor ◽  
Age Related

SynopsisOne hundred and sixty-six unipolar and bipolar out-patients (21–78 years) on long-term lithium treatment were studied on a prospective basis. Although there was a possible tendency for manic attacks to increase in prevalence and severity with age, it was difficult to demonstrate a general age-related decline in lithium efficacy. There was a tendency for the prevalence and severity of fine hand tremor to increase with age. This was not seen with polydipsia/polyuria, the other typical lithium side-effect.

scholarly journals A Double-Edged Sword Role of Cytokines in Prostate Cancer Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Chenyu Mao ◽  
Yongfeng Ding ◽  
Nong Xu
Keyword(s):  
Prostate Cancer ◽  
Immune System ◽  
Side Effects ◽  
Cancer Immunotherapy ◽  
The Other ◽  
Cancer Death ◽  
Other Hand ◽  
High Doses

Prostate cancer (PC) is one of the most common malignancies among men and is the second leading cause of cancer death. PC immunotherapy has taken relatively successful steps in recent years, and these treatments are still being developed and tested. Evidence suggests that immunotherapy using cytokines as essential mediators in the immune system may help treat cancer. It has been shown that cytokines play an important role in anti-tumor defense. On the other hand, other cytokines can also favor the tumor and suppress anti-tumor responses. Moreover, the dose of cytokine in cancer cytokine-based immunotherapy, as well as the side effects of high doses, can also affect the outcomes of treatment. Cytokines can also be determinative in the outcome of other immunotherapy methods used in PC. In this review, the role of cytokines in the pathogenesis of cancer and their impacts on the main types of immunotherapies in the treatment of PC are discussed.

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